Terahertz waves regulate the mechanical unfolding of tau pre-mRNA hairpins

Abstract

Intermolecular interactions, including hydrogen bonds, dominate the pairing and unpairing of nucleic acid chains in the transfer process of genetic information. The energy of THz waves just matches with the weak interactions, so THz waves may interact with biomolecules. Here, the dynamic effects of THz electromagnetic (EM) waves on the mechanical unfolding process of RNA hairpins (WT-30nt and its mutants, rHP, SARS-CoV-2, and SRV-1 SF206) are investigated using steered molecular dynamics (SMD) simulations. The results show that THz waves can either promote the unfolding of the double helix of the RNA hairpin during the initial unfolding phase (4-21.8 THz) or significantly enhance (23.8 and 25.5 THz) or weaken (37.4 and 41.2 THz) its structural stability during unfolding. Our findings have important implications for applying THz waves to regulate dynamic deconvolution processes, such as gene replication, transcription, and translation.

Keywords: Molecular structure; Radiation physics.

Graphical abstract

Figure 1

RNA 2D and 3D structures 3D structures obtained from the initial structures generated online by the Vfold3D tool after Gromacs energy minimization, with different colors drawn by base names (G, C, A, and U are shown in gray, green, white, and pink, respectively). (A) The secondary structure of RNA WT-30nt and the tertiary structure of RNA WT-30nt and +14U used for simulation. The +14 nucleotide C labeled red is substituted with U in the mutation +14U. (B) The secondary structure of RNA +19G-30nt and the tertiary structure of RNA +19G-30nt and +14U+19G-30nt used for simulation. The +14 nucleotide C and +19 nucleotide C labeled in red are substituted with U and G, respectively, in the mutation +14U+19G. (C) The secondary structure and the tertiary structure of RNA rHP used for simulation. (D) Unfolded WT-30nt formed by the unfolding of folded WT-30nt. (E) The secondary structure and the tertiary structure of SF206 used for simulation. (F) The secondary structure and the tertiary structure of SARS-CoV-2 used for the simulation.

Figure 2

The IR absorption spectra of TIP3P water, folded WT-30nt, and unfolded WT-30nt in an aqueous solution The absorbance is normalized. The small box in the upper right corner is the zoomed-in local spectral squares.

Figure 3

The curves of pulling force and unfolding time of WT-30nt with 0.1–3 THz, 0.5 V/nm, y-polarized EM waves All noE in this paper is the control group and represents without THz waves. An average of 20 sets plots all curves of the pulling force.

Figure 4

The curves of the pulling force and unfolding time of WT-30nt with 4–21.8 THz, 0.5 V/nm, y-polarized EM waves An average of 20 sets plots the curves of the pulling force.

Figure 5

Changes in the total number of formed hydrogen bonds (HBs) among base pairs of WT-30nt with 4–21.8 THz, 0.5 V/nm, y-polarized EM waves The WT-30nt structure (Figure 1A) is divided into two symmetric groups (-9G to +7A and +8C to +21C) to analyze the number of hydrogen bonds (30°, within 3.5 Å) between these two groups during mechanical unfolding. An average of 20 sets plots all the curves of HBs.

Figure 6

The effect of 23.8–41.2 THz, 0.5 V/nm, y-polarized EM waves on the WT-30nt mechanical unfolding (A) Normalized energy of the mechanical unfolding process of WT-30nt under the action of THz waves. The dots in the vertical bar of noE are the average of 20 sets, set to 1, and the length of the vertical bar is the standard deviation range of 20 sets. (B) The curves of pulling force and unfolding time of WT-30nt with THz waves. An average of 20 sets plots the curves of the pulling force.

Figure 7

The curves of pulling force and unfolding time of WT-30nt with 23.8 THz, 0.5 and 1.0 V/nm, y-polarized EM waves An average of 20 sets plots the curves of the pulling force. See Figures S6 and S7 for more comparisons.

Figure 8

The curves of pulling force and unfolding time of WT-30nt with 10 THz, 0.5 V/nm, x- and y-polarized EM wave An average of 20 sets plots the curves of the pulling force. Any errorbar is the deviation of the pulling force of 20 sets from the average pulling force, which takes one standard deviation. See Figure S8 for more comparisons.

Figure 9

The curves of pulling force and unfolding time of RNAs pulled along the y direction An average of 20 sets plots the curves of the pulling force. Total SMD time is 2.5 ns. We take a 2 ns (already fully unfolded) data plot.